Table of Content

10 February 2015, Volume 37 Issue 2

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Discussion on the setup requirements of Mtb laboratory

DENG Hai-qing, YANG Lei, CHEN Cheng, WANG Guo-zhi, CHEN Guo-qing

Chinese Journal of Antituberculosis. 2015, 37(2):  117-121.  doi:10.3969/j.issn.1000-6621.2015.02.001

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According to the provisions of “Laboratories-General Requirements for Biosafety” for the biosafety laboratory and “The Test Procedures of Tuberculosis Diagnostic Laboratory” for the Mycobacterium tuberculosis (Mtb) bacteriology testing laboratories, in this paper we explore the basic requirements and shortcomings of the biosafety level Ⅱ(BSL-2) laboratory to offer some suggestions for the biosafety of Mtb bacteriology testing laboratory which can conduct Mtb isolating, culturing, drug susceptibility testing and genotyping and so on. It might contribute to similar settings and peers.

Analyses on resistance to cycloserine and p-aminosalicylic acid and genotypes in multidrug-resistant M. tuberculosis isolates

YANG Jian，PANG Yu，ZHAO Yan-lin，ZHANG Tian-hua，WANG Xi-di，CHEN Mei-ling，LI Yan，WANG Rui

Chinese Journal of Antituberculosis. 2015, 37(2):  122-127.  doi:10.3969/j.issn.1000-6621.2015.02.002

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Objective To evaluate the resistance to cycloserine (Cs) and p-aminosalicylic acid (PAS) in multi-drug resistant (MDR) M. tuberculosis isolates, and analyze the relationship between the genotype and drug-resistant phenotype, which will provide the scientific evidence for MDR-tuberculosis treatment.  Methods One hundred and ninety-six MDR-M.tuberculosis isolates were collected from the first tuberculosis drug resistance survey of China conducted in 2007, were detected their minimum inhibition concentrations (MICs) of Cs and PAS by microplate Alamar blue assay, and were analyzed the genotypes by Spoligotyping method. Cs and PAS resistant rates between Beijing genotype and non-Beijing genotype strains were compared using Chi square test, P<0.05 was considered as statistically significant difference.  Results Of 196 MDR-M. tuberculosis isolates, 22.4%（44/196） were resistant to Cs, and 17.3%（34/196） were resistant to PAS. 82.7%（162/196）isolates belonged to Beijng geno-type, while 17.3%（34/196） strains belonged to non-Beijing genotypes. Of 162 Beijing genotype strains, 21.0% （34/162）strains were resistant to Cs, while 29.4%（10/34） of non-Beijing genotype strains were resistant to Cs. There were no statistical difference in Cs-resistant rates between Beijing and non-Beijing genotype strains（χ²=1.15，P>0.05）. 16.0%（26/162）of Beijing genotype strains were resistant to PAS, while 23.5% (8/34) of non-Beijing genotype strains showed the resistance to PAS. They had no significant difference（χ²=1.10，P>0.05）.  Conclusion The Cs- and PAS-resistant rates in MDR-M. tuberculosis strains were high in China. Beijing genotype was the predominant among MDR-M. tuberculosis isolates in China. The Cs- and PAS-resistant rates between Beijing and non-Beijing genotype strains had no significant difference.

Study on levels of serum retinol and retinol-binding protein-4 in patients with pulmonary tuberculosis

MAI Hong-zhen, YANG Zhi, SONG Xiao-dong, CAI Chun-kui, LU Xi-wei

Chinese Journal of Antituberculosis. 2015, 37(2):  128-133.  doi:10.3969/j.issn.1000-6621.2015.02.003

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Objective To determine the levels of serum vitamin A (retinol) and retinol-binding protein-4 (RBP₄) in drug-resistant pulmonary tuberculosis (PTB), susceptible PTB and healthy people; to analyze the related factors to influence the levels of serum retinol and RBP₄.  Methods Outpatients and inpatients with PTB who received treatment in Dalian TB Hospital from July 2011 to August 2013 were recruited in this study, including 128 drug-resistant PTB patients (drug-resistant group) and 152 susceptible PTB patients (non drug-resistant group). Meanwhile, 120 matched healthy persons who received physical examinations in the same hospital were selected as the control group. The levels of serum retinol and serum RBP₄ among all those recruited subjects were tested. The serum retinol was measured by high-performance liquid chromatography (HPLC) and the serum RBP₄ was measured by enzyme-linked immunosorbent assay (ELISA). The results were showed as x±s and all data were analyzed using SPSS software version 15.0. ANOVA and SNK-q test were used for the comparisons among multi groups. P<0.05 was regarded as statistical significance. Linear correlation and multiple stepwise regression analysis were used for correlated factors analysis of the levels serum retinol and RBP₄.  Results The levels of serum retinol and RBP₄ in drug-resistant group and non drug-resistant group were (206.10±10.35) μg/L, (6.22±1.64) μg/ml and (249.61±12.06) μg/L, (8.23±2.31) μg/ml respectively, which were significantly lower than those in the control group ((326.57±11.52) μg/L and (11.52±2.60) μg/ml) (q=12.35, q=10.66, all P<0.01；q=3.86, q=3.36, all P<0.05); Furthermore, the levels of serum retinol and RBP₄ in drug-resistant group were significantly lower than those in non drug-resistant group (q=3.25, q=3.12, all P<0.05). A multiple stepwise regression analysis showed that body mass index (BMI) was the only independent influencing factor of the levels of serum retinol and RBP₄ (t=2.154, t=5.211, all P<0.05).  Conclusion The levels of serum retinol and RBP₄ significantly decreased in PTB patients and the decrease was more obvious in drug-resistant PTB patients.

Clinical value of the loop-mediated isothermal amplification assay for direct detection of Mycobacterium tuberculosis in the sputum

LI Jin-li，WANG Feng，PENG Yi，HONG Chuang-yue，YANG Ying-zhou

Chinese Journal of Antituberculosis. 2015, 37(2):  134-139.  doi:10.3969/j.issn.1000-6621.2015.02.004

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Objective To evaluate the value of loop-mediated isothermal amplification (LAMP) assay for the detection of Mycobacterium tuberculosis in the sputum.  Methods The sputum samples were collected from 350 patients from The Tuberculosis (TB) Clinic of Shenzhen Center for Chronic Disease Control between April and September 2013, which including 216 cases of TB and 134 cases of pseudophthisis. Of 216 TB patients, 93 were the cases newly diagnosed, including 41 smear-positive cases and 52 smear-negative cases; 123 were the cases follow-up therapy. There are 11 cases with nontuberculous Mycobacterium infection in pseudophthisis. The specimens were simultaneously detected using four methods (smear microscopy, L-J culture, real-time PCR and LAMP). The clinical dia-gnoses were used as the standard method, the sensitivity and specificity of LAMP method in newly diagnosed patients were calculated by SPSS 17.0. The detection efficiency between different methods was compared usingχ² test. P<0.05 was considered as significant difference. The concordance of LAMP and real time PCR method was evaluated by Kappa test.  Results The sensitivities of smear microscopy, L-J culture, LAMP and real-time PCR in newly diagnosed TB patients were 44.1%（41/93）, 52.7%（49/93）, 48.4%（45/93）and 48.4%（45/93）, respectively. There were statistic differences among four methods (P>0.05). The sensitivity of LAMP was 90.2% (37/41) in smear-positive TB patients, while the sensitivity in smear-negative TB patients was 15.4%（8/52）, and the specificity of LAMP was 100.0% (134/134). The positive rates of a single test using smear microscopy, L-J culture, real-time PCR and LAMP for 123 treated patients were 26.0%（32/123）, 14.6%（18/123）, 31.7%（39/123） and 30.9%（38/123）, respectively. The concordance of LAMP and real-time PCR was 96.9%(339/350). The Kappa value was 0.91.  Conclusion LAMP was a specific and simple method for the diagnosis of TB , and the performance of LAMP was high consistency with real-time PCR.

Fast diagnostic value of SAT-TB for smear-negative pulmonary tuberuclosis using bronchoalveolar lavage fluid

FAN Lin, WANG Peng, YANG Yan, MA Jun, GE Yan-ping, WEI Wei, CUI Zhen-ling

Chinese Journal of Antituberculosis. 2015, 37(2):  140-144.  doi:10.3969/j.issn.1000-6621.2015.02.005

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Objective To study the diagnostic value of SAT-TB（simultaneous amplification and testing for Mycobacterium tuberculosis） for smear-negative pulmonary tuberculosis(PTB) by testing bronchoalveolar lavage fluid (BLAF). Methods From June 2012 to June 2014 in Shanghai Pulmonary Hospital Tongji University, we screened 252 suspected PTB patients with 3 consecutive negative sputum smears, and obtained their BLAF specimen by brochchoscopy. BALF was tested by both Bactec MGIT 960 culture and SAT-TB assay. We diagnosed all patients, followed up for at least 6 months and collected associated information of patients regarding final diagnosis, culture results, imaging changes. The sensitivity, specificity, PPV and NPV for each diagnostic test were calculated using culture results as reference standard.  Results Of 234 PTB suspects included in the final analysis, 58 were TB culture positive, 112 were PTB patients by clinical diagnosis with culture negative, 64 were non-TB patients. Using culture confirmed results as reference standard, the sensitivity, specificity, positive predictive value, negative predictive value of SAT-TB for smear-negative PTB testing BALF were 81.0%(47/58, 95%CI：69.0%－90.1%), 96.9%(62/64，95%CI：88.9%－100.0%), 95.9% (47/49，95%CI：86.4%－100.0%) and 84.9%(62/73, 95%CI：75.3%－92.2%). The detection time of SAT-TB was around two hours, remarkably shorter than 31 days needed by culture.  Conclusion SAT-TB can provide reliable, fast diagnostic evidence for smear- negative PTB and is a valuable diagnostic method.

Analysis of serum protein and other related factors of 145 retreated smear positive tuberculosis patients

LIANG Bing, WU Hong, HUANG Bo, WEI Yun-jin, DENG Hong, LIN Yin, SU Jing-yi

Chinese Journal of Antituberculosis. 2015, 37(2):  145-148.  doi:10.3969/j.issn.1000-6621.2015.02.006

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Objective This paper work aims to analyze the nutrition of retreated smear positive tuberculosis patients treated in 2012—2013. In addition, the relationship between malnutrition and tuberculosis retreatment was discussed. Methods We observed nutritional status of the retreated smear-positive patients through measurement of serum protein, erythrocyte count, and hemoglobin of 145 cases of retreated smear positive patients and 105 newly diagnosed smear positive patients during their first visit to Guangzhou Thorax Hospital Clinic Ⅱ. The serum total protein, albumin, globulin, A/G ratio, total number of red blood cells, lymphocyte count, hemoglobin values was compared between new and retreatment patients by using Chi-square test, P<0.05 was considered statistically significant.  Results Among 105 new smear-positive patients, the total protein decreased in 22.86% (24/105) of patients, albumin and globulin reduced in 20.00% (21/105) and 17.14% (18/105) of patients respectively, A/G ratio, red blood cell count, hemoglobin and lymph cells reduced in 34.29% (36/105), 24.76% (26/105), 47.62%（50/105） and 2.86% (3/105) of the patients respectively; Of the 145 retreated patients, the total protein decreased in 22.76%（33/145）of patients, albumin and globulin reduced in 22.76%（33/145） and 24.83%（36/145） of patients respectively, A/G ratio, red blood cell count, hemoglobin and lymph cells reduced in 51.72%（75/145）, 26.90%（39/145）, 33.10%（48/145） and 3.45%（5/145） of the patients respectively; The decreasing proportion of A/G ratio and hemoglobin is statistically significant different between new and retreated patients (χ²=7.502, 5.384, P<0.05). The decreasing proportion of total protein, albumin, globulin, red blood cell count, lymph cells did not show significant different between two groups（χ²=0.000，0.274，2.124，0.144，0.069，P＞0.05）.  Conclusion Lower serum protein A/G ratio is high risk factor of retreatment of tuberculosis.

Analysis of anti-tuberculosis drug susceptibility proficiency test 2009—2013 in China

SONG Yuan-yuan, ZHAO Bing, XIA Hui, ZHAO Yan-lin

Chinese Journal of Antituberculosis. 2015, 37(2):  149-156.  doi:10.3969/j.issn.1000-6621.2015.02.007

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Objective To evaluate and analyze the results of nationwide anti-tuberculosis drug susceptibility proficiency testing from 2009 to 2013, and improve the capability of tuberculosis laboratories in China. Methods Natio-nal tuberculosis reference laboratory issued 30 Mycobacterium tuberculosis isolates for the DST to each participating laboratories yearly from 2009 to 2013. The laboratories performed DST for isoniazid(H), streptomycin(S), ethambutol(E), rifampicin(R), kanamycin(Km), amikacin(Am), capreomycin(Cm) and ofloxacin (Ofx) using the proportion method in Lowenstein-Jensen medium, the World Health Organization guideline was strictly followed. All 508 laboratories participated the proficiency testing and reported the results of first line DST, and 445 laboratories reported the results of second line DST. The reported results were checked and compared with the judicial results by national tuberculosis reference laboratory. The evaluation index is sensitivity, specificity, reproducibility and efficiency. The Chi-square test was be used to analyze the results, and the Cochran-Armitage trend test was be used to describe the trend results, significant difference was defined as P<0.05.  Results The overall value of sensitivity, specificity, reproducibility and efficiency for each drug was respectively as following: H: 91.88%－97.62%, 92.01%－98.33%, 86.55%－95.27% and 91.40%－97.60%；S: 88.79%－94.14%, 87.59%－91.36%, 77.37%－93.13% and 88.20%－92.45%；E：66.24%－85.17%, 83.22%－97.87%, 63.46%－89.76% and 75.78%－90.80%；R: 78.54%－96.34%, 96.19%－98.07%, 79.11%－95.66% and 90.72%－97.21%；Km: 81.12%－95.46%, 95.35%－98.86%, 94.12%－96.84% and 90.23%－97.77%；Am: 93.14%－98.94%, 96.16%－99.00%, 93.52%－97.94% and 95.59%－98.19%；Cm:52.45%－95.68%, 89.68%－97.85%, 89.48%－92.99% and 89.08%－95.61%；Ofx: 84.75%－94.38%, 96.21%－98.90%, 88.01%－94.41% and 93.01%－96.90%. Except for the specificity of S, reproducibility of Km and Cm was not statistically significant difference between each year(χ² value of 8.49, 4.1, 7.78, respectively, P>0.05）,the difference of overall sensitivity for each drug between each year was statistically significant(H:χ²=134.76；S:χ²=44.12；E:χ²=266.22；R:χ²=256.35；Km:χ²=197.46；Am:χ²=12.16；Cm:χ²=433.50；Ofx:χ²=47.38，P<0.05); the difference of overall specificity for other drug between each year was statistically significant(H:χ²=67.69； E:χ²=439.39；R:χ²=16.61；Km:χ²=94.97；Am:χ²=52.96；Cm:χ²=139.51；Ofx:χ²=11.66，P<0.05);the difference of overall reproducibility for other drug between each year was statistically significant(H:χ²=61.82；S:χ²=127.15；E:χ²=246.49；R:χ²=180.03；Am:χ²=21.65；Ofx:χ²=28.49，P<0.05); the difference of overall efficiency for each drug between each year was statistically significant(H:χ²=162.05；S:χ²=36.58；E:χ²=369.11；R:χ²=152.30；Km:χ²=233.69；Am:χ²=32.55；Cm:χ²=168.79；Ofx:χ²=36.97，P<0.05). While, except for the overall sensitivity of Am and Cm, the overall specificity of Ofx and the overall reproducibility of Km, Am and Cm（Z value of 0.46, 0.99, －0.30, －0.85, 0.09 and －0.27, respectively, P>0.05), the overall sensitivity for other drug showed a trend of increase by year (H:Z=－11.06；S: Z=－6.39；E: Z=－12.39；R: Z=－11.17；Km: Z=－12.60；Ofx: Z=－4.40，P<0.05);the overall specificity for other drug showed a trend of increase by year(H:Z=－3.85；S: Z=－2.14；E: Z=－12.30；R: Z=－3.31；Km: Z=－5.05；Am: Z=－5.43；Cm: Z=－8.90，P<0.05); the overall reprodu-cibility for other drug showed a trend of increase by year(H:Z=－5.36；S: Z=－9.11；E: Z=－7.76；R: Z=－8.52；Ofx: Z=－3.44，P<0.05)；the overall efficiency for each drug showed a trend of increase by year (H:Z=－10.95；S: Z=－5.95；E: Z=－11.87；R: Z=－9.70；Km: Z=－14.11；Am: Z=－3.32；Cm: Z=－5.71；Ofx: Z=－3.40，P<0.05).  Conclusion Proficiency testing was an efficient method to improve the capacity and performance of DST, PT has made a great contribution to increase the ability of DST in Chinese TB laboratory network, and continuously conducting the laboratory internal quality control and carrying out personnel training to perform proficiency testing could increase the laboratory capabilities of DST year by year.

A feasibility study on treatment of tuberculous hydrocephalus with early ventriculo peritoneal shunt

ZHAO Ya-qun, LI Hong-min, HE Xiu-yun, WU Xue-qiong, LIU Jiang, XU Mai, WANG Yong, DI Cui-li, TANG Ke

Chinese Journal of Antituberculosis. 2015, 37(2):  157-160.  doi:10.3969/j.issn.1000-6621.2015.02.008

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Objective To explore the clinical feasibility on treatment of patients with tuberculous hydroce-phalus by using early ventriculo peritoneal shunt. Methods A retrospective analysis was conducted. Thirty patients with tuberculous meningitis hydrocephalus who received ventriculo-peritoneal shunt treatment in the 309th Hospital of PLA from 2006 January to 2010 December were included in this study. The enrolled patients were divided into two groups according to whether the intracranial tuberculosis (TB) was controlled or not, namely early (9) or late (21) ventricle-peritoneal shunt group. The following data or information related to the patients were recorded and analyzed: Palur grade, GCS score, postoperative shunt patency and ADL grade. Results All the 9 patients in the early ventriculo-peritoneal shunt group were classified as Palur Grade Ⅲ or Ⅳ, and 7/9 cases had GCS score less than 8 points. Four out of 21 patients in the late group were classified as Palur Grade Ⅲ or Ⅳ, and 1/21 cases had GCS score less than 8 points. One patient in each group occurred shunt tube obstruction after the surgery which resulted in failure of ventriculo-peritoneal shunt treatment and tube drawing. At the end of 12 months after discharged from the hospital, the results of ADL Grade among all patients were as follows: 10 cases (33.33%) were ADL Grade Ⅰ, 5 cases (16.67%) were ADL Grade Ⅱ, 6 cases (20.00%) were ADL Grade Ⅲ, 6 cases (20.00%) were ADL Grade Ⅳ and 3 (10.00%) cases were ADL Grade Ⅴ. Meanwhile, 7/9 patients in the early group reached ADL Grade Ⅰ-Ⅲ while 14/21 patients in the late group reached ADL Grade Ⅰ-Ⅲ. Conclusion This study found that it is feasible to treat the patients with tuberculous hydrocephalus by using early ventriculo-peritoneal shunt when TB in brain has not been cured. The results suggested that regardless of whether the intracranial TB has been controlled or not, early ventriculo-peritoneal shunt did not result in the increased risk of intracranial infection and CSF protein blocking.

Study on the efficacy of antituberculosis regimens containing different dosage of levofloxacin in patients with MDR-TB

WANG Qing-feng, WANG Jun, WANG Jing, DUAN Hong-fei, GE Qi-ping, HUANG Xue-rui, DU Ya-dong, HAN Xi-qin, CHU Nai-hui

Chinese Journal of Antituberculosis. 2015, 37(2):  161-166.  doi:10.3969/j.issn.1000-6621.2015.02.009

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Objective To observe the efficacy of antituberculosis regimens containing different dosage of levofloxacin in the treatment of multidrug-resistant tuberculosis(MDR-TB), and to guide to choose rational dosage of levofloxacin (Lfx) in clinical practice.  Methods One hundred and twenty-five inpatients and outpatients with MDR-TB treated from Jan. 2011 to Nov. 2012 in Beijing Chest Hospital, Capital Medical University were enrolled, and all patients were randomly divided into 3 groups with different dosage of Lfx (400 mg/d-control group, 600 mg/d and 800 mg/d) combined with other anti-tuberculosis agents. Plasma samples were taken to detect plasma drug concentrations at 2 hours after taking Lfx at 7 days’ treatment. The clinical efficacy (sputum negative conversion rate) and adverse effects of the three groups were observed for 12 months. Statistical analysis was performed using the Statistical Package for the Social Sciences(SPSS) for Windows(version 13.0)．Theχ² test was used in the comparison of categorical variables．The Kruskal-Wallis H test was applied in the mean comparison among many groups. P<0.05 was considered statistically significant. Results The rates of sputum conversion for the group of 600 mg/d Lfx at the end of 3, 6, 9 and 12 months were 53.8% (21/39), 56.4% (22/39), 59.0% (23/39) and 59.0% (23/39), which were significantly higher than those of the group of 400 mg/d Lfx (30.0% (12/40), 32.5% (13/40), 35.0% (14/40) and 35.0% (14/40)), respectively. The differences were significant statistically (χ²=4.60, 4.57, 4.95 and 4.95，P<0.05). The rates of sputum conversion of the group of 800 mg/d Lfx (60.0%(24/40), 65.0%(26/40), 65.0%(26/40) and 65.0% (26/40)) were also significant higher than those of the group of 400 mg/d Lfx at the different time of treatment. The differences were also significant statistically (χ²=7.27, 8.46, 7.20 and 7.20, P<0.05). However, the differences of the rates of sputum conversion between the group of 800 mg/d Lfx and 600 mg/d Lfx were not significant with statistics (χ²=0.31, 0.61, 0.21 and 0.21, P>0.05). Gastrointestinal reaction, muscle and joint pain and central nervous system abnormalities were the main performance as adverse reaction in the three groups. The rates of the main adverse reactions were 0.0%, 15.0% (6/40) and 0.0% for the group of 400 mg/d Lfx, 2.6% (1/39), 10.3% (4/39) and 2.6%(1/39) for the group of 600 mg/d Lfx, 5.0% (2/40), 17.5% (7/40) and 7.5%(3/40) for the group of 800 mg/d Lfx. There were no significant differences in adverse reactions among the three groups (χ²=2.04, 0.87 and 3.58, P>0.05).  Conclusion 600 mg/d and 800 mg/d Lfx were better for MDR-TB treatment, but the difference was not statistically significant, so 600 mg/d is recommended for MDR-TB treatment and 800 mg/d can be applied for some cases.

Preliminary clinical study on the related factors in drug-induced liver injury of anti-TB patients

ZHU Wei-shan, ZHANG Bin

Chinese Journal of Antituberculosis. 2015, 37(2):  167-172.  doi:10.3969/j.issn.1000-6621.2015.02.010

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Objective To explore the related factors and clinical characteristics of liver injury in anti-TB patients. Methods The incidence of liver injury in 721 new tuberculosis (TB) cases received treatment from January 1, 2009 to December 30, 2012 in the Department of Infection Disease of Qingpu Branch of Zhongshan Hospital was calculated, the history of liver diseases, age, gender, status of sputum Mycobacterium tuberculosis, history of alcoho-lism, malnutrition, and other related factors were studied and the clinical symptoms, liver damage degree, time of abnormal with/without history of liver diseases were compared and the influences to anti-TB treatment were analyzed as well. SPSS 11.0 was used for data analysis. Theχ² test and logistic method were used in the comparison of categorical variables, P<0.05 was considered statistically significant.  Results Ninety-nine cases of drug-induced liver injury were diagnosed in 721 patients, accounting for 13.7% (99/721). History of liver diseases (27.5% (39/142) vs 10.4% (60/579), χ²=28.16, P<0.01), age (25－ age group: 8.0% (25/311), 40－ age group: 9.7% (24/248), 60－70 age group: 30.9% (50/162); χ²=28.44, P<0.01), alcohol abuse (29.7% (11/37) vs 12.9% (88/684), χ²=8.43, P<0.01) and malnutrition (19.1% (60/314) vs 9.6% (39/407), χ²=13.58, P<0.01) were risk factors by univariate analysis. History of liver diseases (Waldχ²=22.994, P<0.01, OR=3.272, 95%CI: 2.016-5.312), alcohol abuse (Waldχ²=5.390, P<0.05, OR=2.667, 95%CI: 1.165-6.103), elderly (Waldχ²=21.187, P<0.01, OR=2.010, 95%CI: 1.493-2.706) and malnutrition (Waldχ²=4.563, P<0.05, OR=1.692, 95%CI: 1.044－2.742)were more likely to suffer drug-induced liver injury by multivariate analysis. It took longer to recover from liver injury induced by anti-TB drugs for the patients with liver diseases history (24.2% (15/62) vs 64.9% (24/37), χ²=16.054, P<0.01). On the basis of protecting liver treatment, we had to adjust the plan and prolong the chemotherapy compared to the patients without liver diseases history (28.6% (16/56) vs 53.5% (23/43), χ²=6.325, P<0.05). Conclusion History of liver diseases, the elderly, alcohol abuse and malnutrition are risk factors for TB drug-induced liver injury. It is necessary to monitor the liver function closely and adjust the anti-TB treatment regimen timely in order to complete the chemotherapy smoothly.

Effects of positive hepatitis B surface antigen on liver injury induced by anti-tuberculosis drugs

LAI Xiao-yu，HUANG Pei-sheng，LIU Gui-fen

Chinese Journal of Antituberculosis. 2015, 37(2):  173-177.  doi:10.3969/j.issn.1000-6621.2015.02.011

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Objective To explore the effects of positive hepatitis B surface antigen (HBsAg) on liver injury caused by anti-tuberculosis (TB) drugs. Methods One hundred and eight patients with positive HBsAg out of 190 pulmonary TB cases visited the station from February 2010 to January 2014 were enrolled in the observation group, and the other 82 cases with negative HBsAg were in control group. The status of liver function damage and degree of damage after anti-TB treatment of the two groups were compared. SPSS 19.0 was used for data analysis. t test was applied in comparison of quantitative data and Chi-square test was used in the comparison of categorical variables．P<0.05 was considered statistically significant. Results The liver damage rate of observation group (30.56%, 33/108) was significantly higher than that of the control group (12.20%, 10/82), and the difference was statistically significant (χ²=8.974，P<0.05). The liver damage rates of observation group increased with the severing infection of hepatitis B virus (HBV)(singal positive; HBsAg, HBeAb, and HBcAb test positive; HBsAg, HBeAg, and HBcAb test positive), which were 15.52% (9/58), 35.48% (11/31) and 68.42% (13/19) respectively. The differences of the liver damage rates among different degree of HBV infection were significant (HBsAg, HBeAb, and HBcAb test positive vs single positive: χ²=4.623, P<0.05; HBsAg, HBeAg, and HBcAb test positive vs single positive: χ² =1.963, P<0.05; HBsAg, HBeAg, and HBcAb test positive vs HBsAg, HBeAb, and HBcAb test positive: χ²=5.120, P<0.05). The alanine aminotransferase (ALT) and total bilirubin (TBL) of observation group were (394.25±48.39)U/L and (91.83±19.02) μmol/L, which were significantly higher than those of the control group ((247.61±52.48) U/L and (48.15±12.91) μmol/L)(t=19.946,18.828, all P<0.01). The recovery time from liver damage of observation group (28.09±15.32) day was significantly longer than that of the control group (11.26±7.34) day (t=10.004, P<0.01). Conclusion The liver damage induced by anti-TB drugs of patients with positive HBsAg is significantly more serious than that of patients with negative HBsAg, and liver damage aggravates with the severing infection of HBV, so that positive HBsAg has obvious effects on liver damage induced by anti-TB drugs.

Analysis of CT findings between tuberculoma misdiagnosed as peripheral lung cancer and peripheral lung cancer

CHEN Liang, ZHONG Qiu，LIU Wen，QIN Jie, LIANG Bo-tao, GAO Cui-nan, ZHOU Lin

Chinese Journal of Antituberculosis. 2015, 37(2):  178-182.  doi:10.3969/j.issn.1000-6621.2015.02.012

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Objective To investigate CT findings of peripheral lung cancer and tuberculoma misdiagnosed as peripheral lung cancer.  Methods From January 2010 to January 2014, 468 patients with confirmed peripheral lung cancer and 58 patients misdiagnosed as peripheral lung cancer were enrolled in the third affiliated hospital of SUN Yat-sen University. The shape, density, features of enhancement, margin, adjacent lymph nodes and satellite lesions were analyzed retrospectively. The statistical software package SPSS version 20.0 for Windows was used for the statistical analysis. Differences were considered to be statistically significant when P<0.05. Results The mean diameter of tuberculoma (3.37±1.23 cm) was similar to that of peripheral lung cancer (3.52±1.37 cm) (t=1.32，P=0.32). Compared with peripheral lung cancer with gravel-like calcification, smooth edge and satellite lesions(5.13% (24/468), 8.97% (42/468), 10.47% (49/468), respectively) were more commonly found than those of tuberculoma (27.59% (16/58), 15.52% (9/58), 48.28% (28/58), respectively)（χ²=37.04，P<0.01；χ²=15.23，P<0.01；χ²=59.23，P<0.01）. Rough edge and pleural indentation were more commonly seen in peripheral lung cancer (91.03%（426/468）, 25.00%（117/468）, respectively） than those of tuberculoma(84.48%（49/58）,8.62%（5/58）,respectively）（χ²=15.23，P<0.01；χ²=7.77，P<0.01）.  Conclusion Gravel-like calcification, smooth edge and satellite lesions are more commonly found in tuberculoma misdiagnosed as peripheral lung cancer, while rough edge and pleural indentation are more commonly seen in peripheral lung cancer.

Evaluation of personnel and working status on TB control and prevention at community level in Beijing

CHEN Xi, HE Xiao-xin, GAO Zhi-dong, WANG Yan-li, LI Bo, ZHANG Hong-wei, ZHANG Tian-hao, ZHAO Xin

Chinese Journal of Antituberculosis. 2015, 37(2):  183-188.  doi:10.3969/j.issn.1000-6621.2015.02.013

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Objective To investigate the status of community health center staff members who are responsible for TB control and prevention and their working status on management of patients with tuberculosis (TB), to further evaluate the affects of community-based management model on improving case-finding and quality of patients treatment so as to development a community-based TB control model in Beijing. Methods August 2012, a questionnaire investigation was conducted among TB staff members who were from 256 community health centers (in which a community-based TB case-management model has been implemented) of 16 districts/counties (including Xuanwu and Chongwen districts) in Beijing. The questionnaire was designed by Beijing Health Bureau Officers and experts of Beijing Research Institute for Tuberculosis Control. Basic personal information of the TB staff was collected, such as age, educational background, professional position, etc.; staff knowledge, understanding, experience and comments towards the community-based TB case-management were also collected. t test and Chi-square test were used for comparing means and proportions. A total of 270 questionnaires were distributed and all of them were responded and valid. So the effective response rate was 100.0%.  Results Among the 270 community health center TB staffs, the mean age was (35.6±10.3) years; the education level mainly was college degree or below, accounting for 65.2%(176/270); 66.7%(180/270) of health workers at community health centers were assigned to at least three tasks per day related to disease control and prevention; length of working for TB was (5.6±5.6) years and the staff in the suburb community health centers had longer time working for TB, the difference was statistically significant(t=5.01, P=0.026); 46.7%(126/270) of community TB staff were responsible for taking drugs for TB patients from the municipal level and the staff proportion who were doing this work at urban community health centers (90.9%，80/88) was higher than that at rural community health centers (25.3%,46/182), the difference was statistically significant (χ²=102.67, P<0.05); the use of telephone was most common way for TB staff and patients to contact each other, accounting for 99.3% (268/270); 84.1% (227/270) of community health center TB staff reported to work overtime for patients visits; 90.4%(244/270)of community health center TB staff thought they were familiar with medications of the patients; 61.1%(165/270)of community health center TB staff thought the number of community health service facility was inadequate and needs to be increased; 73.0%(197/270)of community health center TB staff thought they need separate rooms, 46.7%(126/270) thought a certain of disinfection facilities were needed and 35.9%(97/270) thought medicine cabinets were needed. Among 270 community health workers who received this investigation, although 98.5% (266/270) of them participated in received or the relevant training organized by their units or high level units, there were still 72.2%(195/270) of them thought the training on psychological rehabilitation and support of TB patients is essential.  Conclusion The education level of TB staff from community health center in Beijing is low and the tasks assigned to them are heavy. The staff working at the suburban community health centers are steady. The urban community health centers provide more services for TB patients on taking anti-TB drugs. The community health services for TB patients needs to be further improved, and the comprehensive training related to TB patients management is needed.

Innate immune recognition of Mycobacterium tuberculosis

WU Xiao-e，CHEN Jing，SONG Shu-xia

Chinese Journal of Antituberculosis. 2015, 37(2):  189-193.  doi:10.3969/j.issn.1000-6621.2015.02.014

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major health problem, with over 2 million deaths each year in the world. Innate immunity plays an important role in the host defense against Mtb. Several classes of pattern recognition receptors (PPRs) expressed on innate immune cells are involved in the recognition of Mtb, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and NOD-like receptors (NLRs). Among the TLR family, TLR2, TLR4, and TLR9 and their adaptor molecule MyD88 play a leading role in the initiation of the immune response against tuberculosis. In addition to TLRs, other PRRs such as NOD2, Dectin-1, Mannose receptor, and DC-SIGN are also involved in the recognition of Mtb. Human epidemiological studies reveal that genetic variation in genes encoding for PRRs in uences disease susceptibility. Therefore, to explore in depth on the recognition characteristics of PRRs and the distribution of gene polymorphism, does not only lead to a better understanding of the pathogenesis of tuberculosis but also may contribute to the design of novel immunotherapeutic strategies.

Progress of pulmonary tuberculosis related microRNAs

YANG La, LI Chang-shan

Chinese Journal of Antituberculosis. 2015, 37(2):  194-198.  doi:10.3969/j.issn.1000-6621.2015.02.015

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Pulmonary tuberculosis is chronic respiratory infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the 2012 World Health Organization (WHO) report, about one third of the global population was infected by Mycobacterium tuberculosis, of which one-tenth people eventually developed with TB disease. China is one of the 22 TB high-burden countries in the world, has about 5 million patients, ranking second in the world. Therefore, TB has become a public health issue in China. Current research is mainly focused on tuberculosis susceptibility genes and immune protection. MicroRNA (miRNA) is a length of about 22 in eukaryotes NT of small non-coding RNA molecules. MiRNA has become the focus of biological research in nearly 20 years, which is linked with the specific site of the target gene mRNA, inhibited the expression of target genes for proteins, regulated its biological development and plays an important role in the development of the disease. Many studies have shown that miRNA play an important role in host-pathogenic immune networks, are also associated with the occurrence and development of bacterial diseases of the lungs. In-depth of miRNA function in TB disease could provide new direction for the diagnosis and treatment of the disease. Therefore, the author summarizes the advances in miRNA associated with tuberculosis, which could create opportunities for TB prevention, diagnosis and treatment.

Progress of TB prevention and control research in students

CHEN Sheng-yu

Chinese Journal of Antituberculosis. 2015, 37(2):  199-202.  doi:10.3969/j.issn.1000-6621.2015.02.016

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As a special group, tuberculosis (TB) in students is easy to spread, and serious ones can cause outbreak. The author retrieved 125 published papers of student TB from 1991 to 2013, reviewed the international and domestic research progress of student TB, discussed and summarized the reason for high incidence, and the pros and cons of screening method, treatment management and preventive therapy, in order to provide the evidence for TB prevention and control work in school.